Efficacy of Empagliflozin and Pioglitazone in Diabetic Patients With NAFLD

PEARL-DM: Efficacy of Empagliflozin and Pioglitazone in Diabetic Patients With NAFLD; Randomized Controlled Trial From Pakistan.

This clinical trial will yield results about the therapeutic effect of combining pioglitazone with SGLT2i in people suffering from NAFLD associated with T2DM. Study participants will be asked to fill out a few questions on proforma that will obtain demographic information as well as information relating to their health. In addition, some blood tests will be done following standard procedures.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Alcoholic Fatty Liver Disease; Type2diabetes
• Intervention / Treatment: Drug: Empagliflozin 10 MG; Drug: Pioglitazone 15mg; Drug: Metformin

Detailed Description

This is a randomized clinical trial conducted to compare the efficacies of pioglitazone and empagliflozin in people suffering from NAFLD associated with T2DM.

Randomization will be done using card randomization. Four different color-coded cards will be kept. Any card will be randomly picked for the patient fulfilling inclusion criteria and will be treated according to the allocated treatment arm mentioned on the card

Written informed consent will be obtained from the immediate attendant of the patient. All ethical considerations will be followed.

Our research has been approved by Jinnah Sindh Medical University, Karachi. For this approval, the investigators have made every effort to ensure the confidentiality of research data collected from all our participants in this survey. The information collected will be stored with the investigators only in the form of de-identified information and will be retained in a secure place under lock and key. Any results that will be generated will be presented on a collective basis, and will not contain the participants name or any other personal details.

Data entry and analysis will be done using SPSS Software version 23. Study analysis will be done using the principle of intention to treat. The mean scores will be compared pre and post-intervention using paired t-test. The association of age, gender, and grade of fatty liver will be compared with different groups using correlation and regression models. All analyses will be at a confidence Interval of 95% and a p-value <.05.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 4

Contacts and Locations

Study Locations

• Pakistan
  • Sindh
    • Karachi, Sindh, Pakistan, 71550
      • Medical ICU, Jinnah Postgraduate Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• T2DM patients with NAFLD glycated
• APRI scores of more than 1.5

Exclusion Criteria:

• Patients having type 1 diabetes
• evidence of advanced/decompensated cirrhosis (on the basis of a Child-Pugh score of more than 7 and MELD of more than 15)
• hepatocellular carcinoma (evidence on ultrasound or alpha-fetoprotein)
• patient suffering from acute or chronic hepatitis
• biliary disease
• HIV
• hemochromatosis
• autoimmune conditions (alpha-1 antitrypsin deficiency, autoimmune hepatitis, Wilson's disease)
• renal dysfunction with GFR [eGFR] <30 mL/min/1.73m2
• history of alcohol ( male >30 g/d and female;20 g/d)
• history of cancer or undergoing treatment for cancer,
• use of amiodarone, tamoxifen, sodium valproate, corticosteroids, methotrexate, ursodeoxycholic acid, S-adenosyl methionine, betaine, silymarin, gemfibrozil
• using supplements including vitamin E, vitamin C, zinc, and selenium or antioxidant agents over the last 3 months
• history of cardiovascular events within the past 3 months
• pregnancy or breastfeeding
• contraindications to empagliflozin use (history of recurrent urogenital infections, current or previous gangrene, or hypersensitivity reaction to the molecule)
• history of bladder cancer
• morbid obesity (BMI greater than 35).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; SOC+ Empagliflozin + Pioglitazone	Drug: Empagliflozin 10 MG; 10-25 mg/day; Drug: Pioglitazone 15mg; 15-45 mg/day; Drug: Metformin; 1000mg-2850mg/ day
Experimental: Group B; SOC +Empagliflozin	Drug: Empagliflozin 10 MG; 10-25 mg/day; Drug: Metformin; 1000mg-2850mg/ day
Experimental: Group C; SOC+ Pioglitazone	Drug: Pioglitazone 15mg; 15-45 mg/day; Drug: Metformin; 1000mg-2850mg/ day
Active Comparator: Group D; SOC only	Drug: Metformin; 1000mg-2850mg/ day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A change in liver steatosis will be assessed through fibro CAP score.	Fibro-controlled attenuation parameter (fibro CAP). The parameter range is commonly between 100 and 400 dB/m, and the greater the reading worse will be the outcome.	Will be assessed at enrollment.
A change in liver steatosis will be assessed through fibro CAP score.	Fibro-controlled attenuation parameter (fibro CAP). The parameter range is commonly between 100 and 400 dB/m, and the greater the reading worse will be the outcome.	Will be assessed at 168th day post enrollment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in SF-36 scores	36-Item Short Form Survey (SF-36) assesses eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. A higher score defines a more favorable health state.	Quality of life will be assessed 84th day post enrollment.
change in SF-36 scores	36-Item Short Form Survey (SF-36) assesses eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. A higher score defines a more favorable health state.	Quality of life will be assessed at day 252 post enrollment.
change in liver fibrosis will be assessed through the FIB-4 index.	Fibrosis-4 index (FIB-4). Low scores will indicate better outcomes (less fibrosis).	at enrollment.
change in liver fibrosis will be assessed through the FIB-4 index.	Fibrosis-4 index (FIB-4). Low scores will indicate better outcomes (less fibrosis).	84th day post enrollment.
change in liver fibrosis will be assessed through the FIB-4 index.	Fibrosis-4 index (FIB-4). Low scores will indicate better outcomes (less fibrosis).	at 168th day post enrollment.
change in liver fibrosis will be assessed through the FIB-4 index.	Fibrosis-4 index (FIB-4). Low scores will indicate better outcomes (less fibrosis).	at day 252 post enrollment.
change in liver fibrosis will be assessed through the APRI Score	AST to platelet ratio index (APRI) Score. Lower the value better the outcome (less fibrosis)	at enrollment.
change in liver fibrosis will be assessed through the APRI Score	AST to platelet ratio index (APRI) Score. Lower the value better the outcome (less fibrosis)	84th day post enrollment.
change in liver fibrosis will be assessed through the APRI Score	AST to platelet ratio index (APRI) Score. Lower the value better the outcome (less fibrosis)	at 168th day post enrollment.
change in liver fibrosis will be assessed through the APRI Score.	AST to platelet ratio index (APRI) Score. Lower the value better the outcome (less fibrosis)	at day 252 post enrollment.
change in liver fibrosis will be assessed through the NFS Score.	NAFLD fibrosis score (NFS). Lower the value better the outcome (less fibrosis)	at enrollment.
change in liver fibrosis will be assessed through the NFS Score.	NAFLD fibrosis score (NFS). Lower the value better the outcome (less fibrosis)	at 84th day post enrollment.
change in liver fibrosis will be assessed through the NFS Score.	NAFLD fibrosis score (NFS). Lower the value better the outcome (less fibrosis)	at 168th day post enrollment.
change in liver fibrosis will be assessed through the NFS Score.	NAFLD fibrosis score (NFS). Lower the value better the outcome (less fibrosis)	at day 252 post enrollment.
Change in hepatic steatosis through the FLI score.	Fatty liver index (FLI). Lower the value better the outcome	at enrollment.
Change in hepatic steatosis through the FLI score.	Fatty liver index (FLI). Lower the value better the outcome	at 84th day post enrollment.
Change in hepatic steatosis through the FLI score.	Fatty liver index (FLI). Lower the value better the outcome	at 168th day post enrollment.
Change in hepatic steatosis through the FLI score.	Fatty liver index (FLI). Lower the value better the outcome	at day 252 post enrollment.
Change in Insulin resistance will be assessed through HOMA-2IR/IR scale.	homeostatic model assessment-2IR (HOMA-2IR/IR). The lower the value better the outcome.	at enrollment.
Change in Insulin resistance will be assessed through HOMA-2IR/IR scale.	homeostatic model assessment-2IR (HOMA-2IR/IR). The lower the value better the outcome.	at 84th day post enrollment.
Change in Insulin resistance will be assessed through HOMA-2IR/IR scale.	homeostatic model assessment-2IR (HOMA-2IR/IR). The lower the value better the outcome	at 168th day post enrollment.
Change in Insulin resistance will be assessed through HOMA-2IR/IR scale.	homeostatic model assessment-2IR (HOMA-2IR/IR). The lower the value better the outcome.	at day 252 post enrollment.
Change in the LFT.	Liver Function test (LFT) such as alanine transaminase, aspartate transaminase, bilirubin, albumin, alkaline phosphatase, gamma-glutamyl transferase .	At enrollment.
Change in the LFT.	Liver Function test (LFT) such as alanine transaminase, aspartate transaminase, bilirubin, albumin, alkaline phosphatase, gamma-glutamyl transferase .	84th day post enrollment.
Change in the LFT.	Liver Function test (LFT) such as alanine transaminase, aspartate transaminase, bilirubin, albumin, alkaline phosphatase, gamma-glutamyl transferase .	at 168th day post enrollment.
Change in the LFT.	Liver Function test (LFT) such as alanine transaminase, aspartate transaminase, bilirubin, albumin, alkaline phosphatase, gamma-glutamyl transferase .	at day 252 post enrollment.
Change in weight	weight. lower the levels better the outcome.	at enrollment.
Change in weight	weight. lower the levels better the outcome.	at 84th day post enrollment.
Change in weight	weight. lower the levels better the outcome.	at 168th day post enrollment.
Change in weight	weight. lower the levels better the outcome.	at day 252 post enrollment.
Change in random blood sugar	random blood sugar	at enrollment.
Change in random blood sugar	random blood sugar.	at 84th day post enrollment.
Change in random blood sugar	random blood sugar.	at 168th day post enrollment.
Change in random blood sugar	random blood sugar. lower the levels better the outcome.	at day 252 post enrollment.
Change in waist circumference	waist circumference. lower the levels better the outcome.	at enrollment.
Change in waist circumference	waist circumference. lower the levels better the outcome.	at 84th day post enrollment.
Change in waist circumference	waist circumference. lower the levels better the outcome.	at 168th day post enrollment.
Change in waist circumference	waist circumference. lower the levels better the outcome.	at day 252 post enrollment.
Change in HbA1c	hemoglobin A1c (HbA1c).lower the levels better the outcome.	at enrollment.
Change in HbA1c	hemoglobin A1c (HbA1c).lower the levels better the outcome.	at 84th day post enrollment.
Change in HbA1c	hemoglobin A1c (HbA1c).lower the levels better the outcome.	at 168th day post enrollment.
Change in HbA1c	hemoglobin A1c (HbA1c).lower the levels better the outcome.	at day 252 post enrollment.
Change in Body mass index	Body mass index. lower the levels better the outcome.	at enrollment.
Change in body mass index	body mass index. lower the levels better the outcome.	at 84th day post enrollment.
Change in body mass index	body mass index. lower the levels better the outcome.	at 168th day post enrollment.
Change in body mass index	body mass index. lower the levels better the outcome.	at day 252 post enrollment.

Collaborators and Investigators

• Sponsor: Jinnah Postgraduate Medical Centre

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: June 16, 2023
• First Submitted That Met QC Criteria: July 11, 2023
• First Posted (Actual): July 12, 2023

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Metformin; Pioglitazone; Empagliflozin
• Other Study ID Numbers: JSMU/IRB/2023/709

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No